Published December 16, 2016 GASTROENTEROLOGY PPIs: Considerations and Resources for Deprescribing in Older Adults Mary Ann E. Zagaria, PharmD, MS, CGPIndependent Senior Care Consultant Pharmacist and President of MZ Associates, Inc.Norwich, New Yorkwww.mzassociatesinc.comPast Chair, Board of Commissioners, Commission for Certification in Geriatric PharmacyRecipient of the Excellence in Geriatric Pharmacy Practice Award from the Commission for Certification in Geriatric Pharmacy US Pharm. 2016;12(41):7-10. With increasing age, there are many factors that make the elderly susceptible to acid-related gastrointestinal disorders.1 In those aged >65, gastroesophageal reflux disease (GERD) is a very common complaint.2 While proton pump inhibitors (PPIs; TABLE 1)—among the most frequently prescribed medications—are highly effective drugs and have revolutionized the management of GERD, evidence supports vigilance about adverse drug effects (ADEs) and the consideration of alternative therapies, if appropriate, in older adults.2-4 GERD is a common disorder in all age groups; however, it is particularly problematic in the elderly.5 The disease often presents with a higher incidence of advanced mucosal damage (i.e., severe esophagitis) and other complications (i.e., bleeding, stenosis, and Barrett’s esophagus) in this vulnerable population.5 Additionally, symptoms are not as reliable an indication of GERD severity in older patients.5 Furthermore, multimorbidity with increasing age and the use of concomitant therapies complicate diagnosis, as well as management, with regard to potential ADEs and drug interactions (DIs).2,5 As a consequence of their ability to significantly suppress acid secretion—through inhibition of the H+/K+ ATPase enzyme system (proton pump) and suppression of the secretion of hydrogen ions into the gastric lumen—PPIs are the preferred class of therapeutic agents for the treatment of GERD.2,6 Essentially, the goals of treatment of GERD in the elderly are the same as those for other age groups: to alleviate symptoms; to heal esophagitis; to manage complications; and to maintain remission.2 PPI use in the elderly has been shown to lead to a number of health concerns.1 Recent data have shown that PPI use is associated with an increased risk of fracture (hip, spine, or wrist fracture, primarily in adults >50 years of age; the greatest risk occurs with high doses or long-term use [>1 year]).1,7 Clostridium difficile infection and diarrhea (with long-term use), community-acquired pneumonia (CAP), vitamin B12 deficiency, hypomagnesemia, and drug interactions are also associated with PPI use.1,7 Outpatient PPI use is associated with a 1.5-fold increased risk of CAP, with the highest risk within the first 30 days after initiation of therapy.3 PPI therapy also increases risk for hospitalization for CAP.3 Healthcare providers need to be vigilant about adverse effects of PPIs, especially in cases where alternative regimens may be available or the benefits of PPI use are uncertain, and consider patient-specific characteristics when PPIs are recommended and/or prescribed to older adults.1,3,4 Hospital-initiated PPI therapy (i.e., for NSAID-induced ulcer, ICU stress-ulcer prophylaxis, Helicobacter pylori) should be reviewed after discharge to confirm an ongoing indication, and a plan should be developed for future review and dose reduction.8 When a patient is receiving a PPI as an integral component of an H pylori eradication regimen (Table 2), the drug may not always be discontinued. The continuation of the PPI prescription is often mistakenly assumed to be for treating GERD. Pharmacists have an opportunity at this juncture to question or verify the indication for use and make appropriate recommendations to avoid keeping the patient on a PPI beyond the time of intended course, thereby reducing the risk of potential ADEs and DIs. Deprescribing PPIs in Older Adults As with ongoing laboratory monitoring and ongoing pain assessment, the ongoing monitoring for whether or not a medication continues to be necessary (i.e., continued need and effectiveness) offers an opportunity for discusion regarding patient preferences; a patient-centered approach to medication therapy management and the process of deprescribing is encouraged. A PPI is a classic example of a medication that may no longer be indicated in an older adult since it is typically indicated for short-term use; other examples are histamine-2 (H2) antagonists and nonsteroidal anti-inflammatory drugs (NSAIDs), for the same reason.9 Polypharmacy may lead to diminished adherence, adverse drug reactions, and increased risk of cognitive impairment, falls, and functional decline.10 The potential benefits of reducing polypharmacy include better health outcomes; fewer hospitalizations; financial savings; and reduced medication administration by nursing staff.11 The process of tapering, stopping, or withdrawing medications that are unnecessary or inappropriate—an effective way to minimize polypharmacy and improve health outcomes—is referred to as deprescribing.12,13 Deprescribing should be limited to one medication at a time; slow tapers allow for gentle physiological adjustments.14 Pharmacists should be aware of those agents commonly associated with discontinuation syndromes, such as PPIs, which upon discontinuation may cause rebound hyperacidity.15 Process guidelines and algorithms have been developed to assist healthcare providers with safe deprescribing.15-18 Patient preferences such as convenience and acceptability should be taken into account when deprescribing is attempted. Furthermore, according to Farrell et al,19 patients and/or caregivers may be more likely to engage if they understand the rationale for deprescribing (i.e., risks of continued PPI use; long-term use may be unnecessary) and the deprescribing process. Beers List Criteria: Minimizing Inappropriate Medication Use The two most widely used explicit criteria regarding inappropriate medication use in older adults are the American Geriatrics Society’s Beers Criteria (AGS Beers)20 and the Screening Tool of Older People’s Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START).20-22 Of note, AGS Beers focus on issues that predominantly affect older adults, while STOPP/START includes selected items that apply to a larger age spectrum.22 Importantly, AGS Beers are not designed for use in hospice or palliative care, whereas STOPP is intended for “most clinical settings.”20,21 PPIs as alternatives to H2 blockers: AGS Beers recommends medication alternatives depending on the patient’s condition/diagnosis. With regard to dementia and cognitive impairment, the PPIs are considered alternative agents to the H2 blockers, which may cause central nervous system (CNS) side effects, mainly confusion, even with slight accumulation related to creatinine clearance.7,20 Avoiding long-term use of PPIs: Independent of condition or diagnosis, AGS Beers note that long-term use of PPIs is potentially inappropriate for patients >65 years in light of increased risk of C difficile infection, bone loss, and fractures; further, it is recommended that treatment duration >8 weeks should be avoided unless benefits outweigh risks.7,20 Guidelines and Algorithms for Deprescribing A 10-step, evidence-based deprescribing guide, with the aim of reducing medication use and decreasing the number of prescribed inappropriate medications, was created by Scott, Gray, et al in 2013.17 In 2015, Scott, Hilmer, et al published a basic five-step deprescribing protocol in conjunction with an algorithm.18 More specific to the discussion of this article, Farell et al recently created evidence-based clinical practice guidelines, with the Ontario Pharmacy Research Collaboration (OPEN), to support clinicians in safely reducing or stopping PPIs and monitoring the their effect.19 Specific to the long-term care setting, Liu and Campbell developed a tip sheet for healthcare providers entitled “Tips for Deprescribing in the Nursing Home.”14 For additional information on the effect of a PPI deprescribing guideline on drug usage and costs in long-term care, consult Reference 23. Prescribing Cascade Although deprescribing is an important component of geriatric practice, it is often overlooked, owing to a healthcare provider’s time constraints.24 As a result, unnecessary medications often go unidentified and may elicit symptoms seen in the elderly that are commonly caused by medications (e.g., dizziness, falls, confusion, weight loss, constipation, delirium) but are not recognized as actual adverse drug reactions.12 This scenario consequently may provoke the addition of a subsequent medication—instead of discontinuing the offending one—to treat that adverse effect. Prescribing cascades such as this may involve PPIs; for example25: Pharmacists should be cognizant of medications added to a patient’s medication regimen subsequent to a symptom that may be attributed to a current medication in the regimen. A heightened awareness of prescribing cascades can help reduce polypharmacy through the process of deprescribing and, ideally, prevent it. Conclusion Patient-specific characteristics should be considered when PPIs are recommended and/or prescribed to older adults in light of the resultant health concerns and risks associated with their use. Becoming familiar with the deprescribing process through available resources can assist with minimizing medication-related geriatric presentations, and thus minimize and prevent subsequent medication intervention in these presentations. Deprescribing PPIs should always take into account patient preferences, for a patient-centered approach. REFERENCES 1. Desilets AR, Asal NJ, Dunican KC. Considerations for the use of proton-pump inhibitors in older adults. Consult Pharm. 2012; 27(2):114-120.2. Calabrese C, Fabbri A, Di Febo G. Long-term management of GERD in the elderly with pantoprazole. Clin Interv Aging. 2007;2(1):85-92.3. Lambert AA, Lam JO, Paik JJ, et al. Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis. 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